1. Technical Field
This invention relates to medicaments containing Concentrated Fluid (CF) extracts from tissues derived from various plant species particularly those which have been chemotaxonomically identified as a species of Agauria, Artemenisia, Camellia, Galphimia, Notopterygium, Pisum, Phyllanthrus, Rhodendron, Taxus, Panax, Ginko, Symphytum, Aloe and Waldstenia. The invention also covers tissue propagated by any means, including culturing of callus cells and optimal horticultural/harvesting methods and polyphase fluid-extraction processes for recovery of bioactive plant secretions such as phytoalexins which result from immediate, optimized processing of freshly-harvested plant tissues. The invention also covers processes for innoculating living plants or cultured tissues derived from herbal plants with endophytic organisms, i.e., symbiotic parasites such as yeasts, fungus, etc. for the purpose of increasing the total amount of extractable, bioactive components. The invention also covers preparation of mammalian medicaments in various forms including oral, topical, parenteral, transdermal, transmucosal, aerosol, liposomes, suspensions, emulsions, etc. The invention also covers methods for use of the several medicaments and forms for therapy on humans and other mammals.
2. General Background
A. Traditional Chinese Herbal Remedies PA0 B. CF Taxus Extracts, CFTAXE PA0 C. CF Aloe Extracts, CFALOE PA0 D. CF Panax Extracts, CFPANE PA0 E. CF Symphytum Extracts, CFSYME PA0 F. CFTE Extracts From Other Plant Species.
Classic Chinese herbal medicine references report soaking, under room conditions (approx. 20 C, and 100 kPa, in an air environment), of dried leaves or roots of many herbal plants. A few modern scientific studies have identified saponins, galactosides, polysaccharides, etc. as being present in herbal cures derived from plant parts of unknown age and dried by various methods; the usual purpose of such studies is to compare clinical testing results of "Chinese herbal extracts" with modern synthetic drug compounds. Remarkably, no reference could be found for harvesting herbal plants at a specific stage of growth/maturity into closed protective vessels for immediate processing/ extraction. According to Chinese tradition, slow air drying in full sunlight is a typical part of the procedure. Liquid-nutrient-media and cell-culture methods for plant cells cannot be found in any reference work for homeopathic medicine. No references can be found to studies of selective breeding and horticulture of herbal plants to maximize either: (a) the levels of bioactive constituents in their tissue just prior to harvest or (b) the amount and number of bioactive constituents generated/secreted by the tissue of herbal plants in response to specific preextraction processing steps such as mechanical injury to cell walls, e.g., by comminuting plant tissue to a selected size range. This is not unexpected, since the basic research in the fields of chemotaxonomy, herbal-plant genetics, and plant-tissue response to injury or other stress is now in its infancy.
Taxines, baccatins, and taxol are the principal medicinal constituents which can be extracted from tissue and plant elements of species identified chemotaxonomically as T. baccata, T. brevifolia, T. canadensis, T. chinesis, T. cuspidata, T. floridana and other wild or non- wild types. Extractable plant elements include flowers, seeds, needles, leaves, buds, nuts, cones, blooms, branches, stems, bark, phloem-cambrial layer and roots. The alkaloids in extracts are poisonous to humans and animals if taken internally; typical symptoms include GI irritation, and failure of circulatory and respiratory functions. Experimental parenteral "taxol" preparations (developed by chemical modification and synthesis) are also believed to be useful, along with other known radiation and chemotherapy technics, for treatment of certain tumors. Since 1989, EPA and environmental groups have targeted firms harvesting bark from the Pacific yew for protests and legal actions; these disputes have essentially halted research on yew-bark-derived taxol in USA.
No publications on: (a) poly- phase, fluid- extraction processes or (b) fine-disperse mammalian therapeutic forms can be found for extracts of plant tissue derived from any Taxus- type plant.
Aloin, is the principal medicinal constituent of thickened, leaf- cell fluid of Aloe species identified chemotaxonomically as A. perryi, or A. vera and other wild or non- wild types; the other constituents include resin, emodin and a mixture of volatile oils. Extractable plant components include flowers, seeds, leaves, anthers, buds, blooms, stems and roots. Aloin isolates administered orally are known for cathartic and purgative use. According to the lore of herbal medicine, "aloe extacts" are useful for skin care and moisturization.
No publications on: (a) poly- phase, fluid- extraction processes or (b) fine-disperse mammalian therapeutic forms can be found for extracts of plant tissues derived from any Aloe- type plant.
Curative powers of ethanol extracts of dried roots of Panax species such as P. japonicus, P. notoginseng, P. shinseng, and P. quinquefolium have been known for many years in the lore of folk medicine from China, Japan and Korea. According to some Oriental practitioners, Panax-based healing formulations prepared by traditional practice can be used to treat most maladies known to man.
No publication can be found which describes Panax plant, or plant-tissue, culture/breeding/harvesting, Panax cultivars/hybrid species, Panax chemotaxonomy; no literature can be found on optimization of any of these factors for preparation of medicaments based upon bioactive species extracted from freshly-harvested Panax plant tissues including, leaves, roots, stems, petioles, buds, flowers, pollen, callus cells, etc. Similarly, no publication can be found which describes sophisticated harvesting methods/timing for maximum yield of therapeutic constitients from Panax tissue such as roots, rhizomes, or rootlets/hairs. Likewise no publication can be found which describes preservation of therapeutic constituents against degradation and oxidation during drying of any plant tissue. Further, no publication can be found on processing or extraction of freshly-harvested Panax plant tissues in a controlled environment with liquid and vapor-phase fluids.
Ethanol or propylene glycol extract solutions of "dried comfrey roots and leaves" are known wound-healing agents as used in topical preparations. As with all medicinal or herbal plants, the actual chemical constituents of in-vivo plant parts are highly dependent upon the genome, plant maturity at harvest, available soil moisture and nutrients, and environmental factors such as infestation by fungus/insects, pollution and climate parameters such as growth- season degree days and freedom from disease, fungus and insect infestation. Classic herbal medicine references give no definite values for the actual level of specific or identified active components in the resulting extracts; neither do they give any indications as to the probability of dangerous impurities and contaminants which may also be present. Indeed, the recipes for "comfrey poultices, plasters, and curative teas" typically do not even confirm the solubility of "active components" in the actual extract solvent solution at any temperature. No references can be found for liquid-nutrient, cell-culture methods for propagation of Symphytum tissue and recovery of bioactive components.
This continuing and profound lack of specificity concerning how to grow and harvest selected plant types, which plant parts to extract, how to do the extraction to get optimal or efficient therapeutic concentrations is no doubt responsible for the various "comfrey" controversies such as poisoning of humans and animals due to pyrrolizidine alkaloids. For products marketed in USA, the FDA has determined that no therapeutic claims can be made for any old-type "comfrey" compositions which have not been subjected to comprehensive lab/animal/and clinical validations according to detailed IND and NDA procedures.
Ethanol extracts of dried roots and leaves of other herbal species including Artemenisia, Camellia, Galphimia, Ginko, Notopterygium, Phyllanthrus, Rhodendron, Teucrium and Waldstenia are portrayed to have various curative and prophylactic properties according to traditional Chinese folk medicine. As already noted above in the case of Panax, no scientific literature is available on cell-culture propagation, plant breeding, optimal horticulture methods, improved harvesting methods/systems, rationalized extraction for freshly-harvested plant elements, modern drug formulations and fine-dispersed physical forms of medicaments, e.g., liposomes, aerosols, emulsions, transdermal patches which have superceded traditional plasters and poultices.